In Vitro Characterization of a Liposomal Formulation of Celecoxib Containing 1,2-Distearoyl-sn-Glycero-3-Phosphocholine, Cholesterol, and Polyethylene Glycol and its Functional Effects Against Colorectal Cancer Cell Lines


ERDOG A., Limasale Y. D. P. , KESKİN D. , TEZCANER A. , BANERJEE S.

JOURNAL OF PHARMACEUTICAL SCIENCES, cilt.102, ss.3666-3677, 2013 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 102 Konu: 10
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1002/jps.23674
  • Dergi Adı: JOURNAL OF PHARMACEUTICAL SCIENCES
  • Sayfa Sayıları: ss.3666-3677

Özet

Nanosized liposomal drug delivery systems are well suited for selective drug delivery at tumor sites. Celecoxib (CLX) is a highly hydrophobic cyclooxygenase-2 inhibitor that can reduce the incidence of colorectal polyps; however, the adverse cardiovascular effects limit its applicability. Here, we report a liposomal formulation of CLX using 1,2-Distearoyl-sn-glycero-3-phosphocholine, cholesterol, and polyethylene glycol. Encapsulation efficiency of the drug was greater than 70%; the release was slow and sustained with only 12%-20% of CLX released in the first 12h. Flow cytometry and confocal microscopy studies using the colon cancer cell lines HCT-116 and SW620 showed significantly higher cellular association and internalization of the liposomes after incubation for 6h when compared with 30min. The liposomes did not colocalize with transferrin, but had a punctuate appearance, indicating vesicular localization. Cell proliferation was inhibited by 95% and 78%, respectively, in SW620 and HT29 cells after incubation with 600M liposomal CLX for 72h. Moreover, cellular motility, as shown by a scratch wound healing assay, was also significantly (p=0.006) inhibited when SW620 cells were incubated with 400M liposomal CLX. This is the first report of the successful encapsulation of CLX in a long-circulating liposomal formulation that could be effective against colorectal cancer. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:3666-3677, 2013